Evaluation of Multiple Models to Distinguish Closely Related Forms of Disease Using DNA Microarray Data: an Application to Multiple Myeloma
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Johanna Hardin
Motivation: Standard laboratory classification of the plasma cell dyscrasia monoclonal gammopathy of undetermined significance (MGUS) and the overt plasma cell neoplasm multiple myeloma (MM) is quite accurate, yet, for the most part, biologically uninformative. Most, if not all, cancers are caused by inherited or acquired genetic mutations that manifest themselves in altered gene expression patterns in the clonally related cancer cells. Microarray technology allows for qualitative and quantitative measurements of the expression levels of thousands of genes simultaneously, and it has now been used both to classify cancers that are morphologically indistinguishable and to predict response to therapy. It is anticipated that this information can also be used to develop molecular diagnostic models and to provide insight into mechanisms of disease progression, e.g., transition from healthy to benign hyperplasia or conversion of a benign hyperplasia to overt malignancy. However, standard data analysis techniques are not trivial to employ on these large data sets. Methodology designed to handle large data sets (or modified to do so) is needed to access the vital information contained in the genetic samples, which in turn can be used to develop more robust and accurate methods of clinical diagnostics and prognostics.Results: Here we report on the application of a panel of statistical and data mining methodologies to classify groups of samples based on expression of 12,000 genes derived from a high density oligonucleotide microarray analysis of highly purified plasma cells from newly diagnosed MM, MGUS, and normal healthy donors. The three groups of samples are each tested against each other. The methods are found to be similar in their ability to predict group membership; all do quite well at predicting MM vs. normal and MGUS vs. normal. However, no method appears to be able to distinguish explicitly the genetic mechanisms between MM and MGUS. We believe this might be due to the lack of genetic differences between these two conditions, and may not be due to the failure of the models. We report the prediction errors for each of the models and each of the methods. Additionally, we report ROC curves for the results on group prediction.Availability: Logistic regression: standard software, available, for example in SAS. Decision trees and boosted trees: C5.0 from www.rulequest.com. SVM: SVM-light is publicly available from svmlight.joachims.org. Naïve Bayes and ensemble of voters are publicly available from www.biostat.wisc.edu/~mwaddell/eov.html. Nearest Shrunken Centroids is publicly available from http://www-stat.stanford.edu/~tibs/PAM.
©2011 Walter de Gruyter GmbH & Co. KG, Berlin/Boston
Artikel in diesem Heft
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- Linear Models and Empirical Bayes Methods for Assessing Differential Expression in Microarray Experiments
- Asymptotic Optimality of Likelihood-Based Cross-Validation
- Using Importance Sampling to Improve Simulation in Linkage Analysis
- Model-Based Assignment and Inference of Protein Backbone Nuclear Magnetic Resonances
- Error-Rate and Decision-Theoretic Methods of Multiple Testing: Which Genes Have High Objective Probabilities of Differential Expression?
- Evaluation of Multiple Models to Distinguish Closely Related Forms of Disease Using DNA Microarray Data: an Application to Multiple Myeloma
- Saturation and Quantization Reduction in Microarray Experiments using Two Scans at Different Sensitivities
- Combining Nearest Neighbor Classifiers Versus Cross-Validation Selection
- Multiple Testing. Part I. Single-Step Procedures for Control of General Type I Error Rates
- Multiple Testing. Part II. Step-Down Procedures for Control of the Family-Wise Error Rate
- Augmentation Procedures for Control of the Generalized Family-Wise Error Rate and Tail Probabilities for the Proportion of False Positives
- Calculating the Statistical Significance of Changes in Pathway Activity From Gene Expression Data
- A Family-Based Association Test for Repeatedly Measured Quantitative Traits Adjusting for Unknown Environmental and/or Polygenic Effects
- Deletion/Substitution/Addition Algorithm in Learning with Applications in Genomics
- Classifying Gene Expression Profiles from Pairwise mRNA Comparisons
- Hierarchical Bayesian Neural Network for Gene Expression Temporal Patterns
- A Mixed Model Approach to Identify Yeast Transcriptional Regulatory Motifs via Microarray Experiments
- Mammalian Genomes Ease Location of Human DNA Functional Segments but Not Their Description
- On the Dependence Structure of Sequence Alignment Scores Calculated with Multiple Scoring Matrices
- Increasing Power for Tests of Genetic Association in the Presence of Phenotype and/or Genotype Error by Use of Double-Sampling
- A Method for Evaluating the Impact of Individual Haplotypes on Disease Incidence in Molecular Epidemiology Studies
- Statistical Methods for Identifying Conserved Residues in Multiple Sequence Alignment
- MergeMaid: R Tools for Merging and Cross-Study Validation of Gene Expression Data
- Sparse Inverse of Covariance Matrix of QTL Effects with Incomplete Marker Data
- Maximum Likelihood for Genome Phylogeny on Gene Content
- Confidence Levels for the Comparison of Microarray Experiments
- PLS Dimension Reduction for Classification with Microarray Data
- Statistical Analysis of Genomic Tag Data
- Statistical Analysis of Adsorption Models for Oligonucleotide Microarrays
- Statistical Significance Threshold Criteria For Analysis of Microarray Gene Expression Data
- A Compendium to Ensure Computational Reproducibility in High-Dimensional Classification Tasks
- Validation and Discovery in Markov Models of Genetics Data
- Making Sense of High-Throughput Protein-Protein Interaction Data
- Reader's Reaction
- Reader Reaction
- Response to Foulkes and De Gruttola
- Software Communication
- BayesMendel: an R Environment for Mendelian Risk Prediction
- Letter to the Editor
- Concerns About Unreliable Data from Spotted cDNA Microarrays Due to Cross-Hybridization and Sequence Errors
Artikel in diesem Heft
- Article
- Using Alpha Wisely: Improving Power to Detect Multiple QTL
- Relating HIV-1 Sequence Variation to Replication Capacity via Trees and Forests
- Linear Models and Empirical Bayes Methods for Assessing Differential Expression in Microarray Experiments
- Asymptotic Optimality of Likelihood-Based Cross-Validation
- Using Importance Sampling to Improve Simulation in Linkage Analysis
- Model-Based Assignment and Inference of Protein Backbone Nuclear Magnetic Resonances
- Error-Rate and Decision-Theoretic Methods of Multiple Testing: Which Genes Have High Objective Probabilities of Differential Expression?
- Evaluation of Multiple Models to Distinguish Closely Related Forms of Disease Using DNA Microarray Data: an Application to Multiple Myeloma
- Saturation and Quantization Reduction in Microarray Experiments using Two Scans at Different Sensitivities
- Combining Nearest Neighbor Classifiers Versus Cross-Validation Selection
- Multiple Testing. Part I. Single-Step Procedures for Control of General Type I Error Rates
- Multiple Testing. Part II. Step-Down Procedures for Control of the Family-Wise Error Rate
- Augmentation Procedures for Control of the Generalized Family-Wise Error Rate and Tail Probabilities for the Proportion of False Positives
- Calculating the Statistical Significance of Changes in Pathway Activity From Gene Expression Data
- A Family-Based Association Test for Repeatedly Measured Quantitative Traits Adjusting for Unknown Environmental and/or Polygenic Effects
- Deletion/Substitution/Addition Algorithm in Learning with Applications in Genomics
- Classifying Gene Expression Profiles from Pairwise mRNA Comparisons
- Hierarchical Bayesian Neural Network for Gene Expression Temporal Patterns
- A Mixed Model Approach to Identify Yeast Transcriptional Regulatory Motifs via Microarray Experiments
- Mammalian Genomes Ease Location of Human DNA Functional Segments but Not Their Description
- On the Dependence Structure of Sequence Alignment Scores Calculated with Multiple Scoring Matrices
- Increasing Power for Tests of Genetic Association in the Presence of Phenotype and/or Genotype Error by Use of Double-Sampling
- A Method for Evaluating the Impact of Individual Haplotypes on Disease Incidence in Molecular Epidemiology Studies
- Statistical Methods for Identifying Conserved Residues in Multiple Sequence Alignment
- MergeMaid: R Tools for Merging and Cross-Study Validation of Gene Expression Data
- Sparse Inverse of Covariance Matrix of QTL Effects with Incomplete Marker Data
- Maximum Likelihood for Genome Phylogeny on Gene Content
- Confidence Levels for the Comparison of Microarray Experiments
- PLS Dimension Reduction for Classification with Microarray Data
- Statistical Analysis of Genomic Tag Data
- Statistical Analysis of Adsorption Models for Oligonucleotide Microarrays
- Statistical Significance Threshold Criteria For Analysis of Microarray Gene Expression Data
- A Compendium to Ensure Computational Reproducibility in High-Dimensional Classification Tasks
- Validation and Discovery in Markov Models of Genetics Data
- Making Sense of High-Throughput Protein-Protein Interaction Data
- Reader's Reaction
- Reader Reaction
- Response to Foulkes and De Gruttola
- Software Communication
- BayesMendel: an R Environment for Mendelian Risk Prediction
- Letter to the Editor
- Concerns About Unreliable Data from Spotted cDNA Microarrays Due to Cross-Hybridization and Sequence Errors
